Nuclear magnetic resonance (NMR) whole body imaging is becoming a valuable non-invasive diagnostic tool in medicine. Early in vitro research has demonstrated the ability of NMR parameters to distinguish abnormal and cancerous tissues from normal tissues in animals and humans. It also revealed a "systemic effect" of tumors, which caused an uptake of water in uninvolved surrounding tissues and even distant organs of tumor bearing animals, thereby reducing NMR differences between the tumor and normal tissues around it. This systemic effect is especially evident in breast cancer, where it reduces the ability of in vitro and imaging methods to distinguish the extent of cancerous lesions in animals models and in human scans. There is a need to enhance NMR distinction of tumors from surrounding tissues to aid in spatial localization, surgical judgements and the monitoring of clinical treatments. Current investigations of chemical agents such as paramagnetic ions and stable free radicals as NMR contrast agents do not address their inability to differentially alter normal and tumor tissue parameters. Such agents primarily affect the relaxation parameters of the extracellular fluids and mainly in crease the distinction of high blood flow organs or organs in which they are sequestered. These agents are also unfortunately expensive, extremely toxic in humans, and have been implicated in mechanisms of carcinogenesis. In this proposal an alternative path is pursued to achieve enhanced NMR contrast in cancer diagnosis. Safe and relatively mild clinical procedures will be tested which (a) alter intracellular water content, (b) increase cell lipid content, or (c) cause reversible disorganization of the cellular macromolecluar lattice, and thereby differentially alter normal and tumor cell NMR parameters by virtue of the different physiological responsiveness of such cells. Agents such as diuretics, estrogen hormones, high lipid diets, and colchicine will be screened in the mouse mammary cancer model using an IBM PC 10 MHz NMR spectrometer. Pilot studies have shown that as much as a 250% enhancement of NMR contrast is possible by such methods. The most promising agents will be further tested in an in vivo Bruker imaging system available at Baylor College of Medicine. Within 3 years, it should be possible to make recommendations for FDA approved, clinically safe, methods to increase the distinction of human breast cancers from normal tissues by whole body NMR Imaging machines.